Gene of eukaryotic cell is regularly stored in histone core which is a basic protein. Histone core is formed from four kinds of proteins called H2A, H2B, H3 and H4 and gene of about 200 bp is wound and stored in a form of a coil in one histone. The gene which is wound around the histone core is connected continuously to form a chromatin fiber (a nucleosome structure). Histone core and gene are regularly wound by an interaction on the basis of polyion complex by cationic moiety of basic protein of the histone core and anionic moiety of the gene.
The gene in such a nucleosome structure forms a stable complex with the histone core whereby the transcription is suppressed. However, as a result of bonding of the transcription factor, a histone acetyltransferase (HAT) is recruited and an amino group of lysine of a basic protein forming the histone core is acetylated whereby the positive charge of the basic protein is neutralized and the nucleosome structure of chromatin is released and disintegrated. In the gene released from the histone core, transcription becomes activated. In the structure of such a chromatin fiber, protein of the histone core having a positive charge and the gene having a negative charge form a statically stable complex and stores the gene therein. When transcription becomes necessary, the basic protein of the histone core is acetylated whereby the positive charge of the basic protein is neutralized and a static formation of complex of the histone core and the gene is disintegrated to activate the transcription.
Incidentally, in recent years, various kinds of gene therapy such as an antisense method or a gene transfer method have been developed. With regard to a method for the transfer of gene into a cell, utilization of virus, etc. has been adopted because of its efficiency but problems in terms of safety have been pointed out. For example, owing to the method, some people were dead in the Unites States. In place of above method, various methods have been developed where lipid or polymer having positive charge is subjected to a static interaction with gene having negative charge and the resulting complex is transferred into the cell.
In those methods however, it is necessary to make the complex more stable to increase the efficiency of transfer into the cell while, on the other hand, transcription of gene is suppressed when it remains complex. Therefore, in order to increase the efficiency of the gene expression transferred into the cell, it is necessary to satisfy the contradictory condition such that the complex transferred into the cell is quickly disintegrated to be in a state of a transferable gene. Consequently, the efficiency of gene transfer in the already-known methods is quite low.
Accordingly, there has been a demand for the development of a complex in which, in a normal state, a stable complex is formed and the gene is stably held there and, in a state where activation of the gene is necessary, the complex is quickly disintegrated and the gene is released therefrom.